Nasal administration of drugs has long been commonly used as a method for administering drugs with local effects such as in rhinitis treatments. However, nasal administration has also drawn attention as an administration route for drugs with systemic effects, for example, peptide/protein drugs such as insulin and calcitonin, and low molecular-weight drugs such as morphine. The reasons include the facts that nasal mucosa has well-developed vascular plexus and is histologically advantageous for drug absorption, drugs absorbed through nasal mucosa can avoid first-pass metabolism in the gastrointestinal tract and liver, and self administration is easy and painless.
Methods for nasal drug administration include, for example, methods in which a drug is dissolved and the resulting liquid or suspension is administered and methods in which a drug is administered as a powdery preparation. In the market, nasal drugs in liquid form are more common than powdery nasal preparations. However, Ishikawa et al. have reported that powdery preparations are superior to liquid preparations in drug retention in a nasal cavity and thus show improved nasal drug absorption (Non-Patent Document 1). The same tendency has also been observed in the present inventors' studies. Also, in order to nasally administer a powdery drug preparation and achieve effective absorption and drug efficacy, it is preferable to administer the preparation in combination with a carrier. Many effective carriers have been reported. For example, divalent metal ions such as calcium with an average particle diameter of 250 μm or less have been disclosed as carriers for nasal administration (Patent Document 1).
Also, according to a report (Patent Document 3), nasal drug absorption of a formulation containing water-absorbing and water-insoluble base such as crystalline cellulose was improved by combining it with a water-absorbing and gel-forming base such as hydroxypropyl cellulose, in comparison with a formulation containing crystalline cellulose alone (Patent Document 2). Meanwhile, the present inventors have reported that when used alone, crystalline cellulose of a particular particle size distribution enables efficient absorption of drugs, such as insulin, through nasal mucosa (Patent Documents 4, 5, and 6).
Generally, required amounts of said effective powdery nasal preparations are delivered into the nasal cavity by methods, such as those that use a single-dose nasal administration device or the like utilizing capsules or blister packs which are filled by an automatic filling machine (Patent Documents 7 and 8) or those that use a multiple-dose nasal administration device or the like containing a drug reservoir filled with the preparation and, at the time of use, a single dose amount is measured from the reservoir and dispensed in a small chamber and delivered into the nasal cavity (Patent Document 9).    Non-Patent Document 1: International Journal of Pharmaceutics, 224, 105-114, 2001    Patent Document 1: Japanese Patent Application Kokai Publication No. (JP-A) H08-27031 (unexamined, published Japanese patent application)    Patent Document 2: JP-A (Kokai) S59-163313    Patent Document 3: JP-A (Kokai) H10-59841    Patent Document 4: International Patent Application Publication WO 03-004048 pamphlet    Patent Document 5: JP-A (Kokai) 2003-206227    Patent Document 6: International Patent Application Publication WO 2006/016530 pamphlet    Patent Document 7: JP-A (Kokai) H08-206208    Patent Document 8: JP-A (Kokai) 2003-154006    Patent Document 9: JP-A (Kokai) 2003-175103